Field of the Invention
The present invention relates to a compound represented by general formula (I):
(wherein all symbols are as defined below), a salt or N-oxide of the compound, or a solvate or prodrug of the compound or the salt or N-oxide (hereinbelow, may be sometimes abbreviated as “the compound according to the present invention”).
Background of Art
Prostaglandin E2 (hereinbelow, abbreviated as “PGE2”) is known as a metabolite in the arachidonate cascade, and is also known to have a cell protection effect, an oxytocic effect, an algogenic effect, an effect of promoting the peristaltic movement of the digestive tract, an awakening effect, a gastric acid secretion inhibiting effect, a blood pressure lowering effect, a diuretic effect and the like.
PGE2 receptors are classified into four subtypes having different roles from one another, i.e., EP1, EP2, EP3, EP4. PGE2 has a wide variety of physiological activities, and therefore has such a problem that, when used as a drug, other undesirable action may be caused besides the intended action. Therefore, it has been attempted to overcome the problem by examining the physiological functions and the expressing sites of the individual subtypes and producing a compound that is effective only on a specific subtype, i.e., a so-called subtype-specific agonist.
For example, an EP2 receptor is considered to be involved in the inhibition of the production of TNF-α and the enhancement of the production of IL-10, and therefore a selective EP2 agonist is considered to be useful for the prevention and/or treatment of immune diseases, allergic diseases, neuronal death, dysmenorrhea, premature birth, miscarriage, baldness, ocular diseases, erectile dysfunction, arthritis, lung injury, pulmonary fibrosis, pulmonary emphysema, bronchitis, chronic obstructive pulmonary disease, liver injury, acute hepatitis, cirrhosis, shock, nephritis, renal failure, cardiovascular diseases, systemic inflammatory response syndrome, sepsis, hemophagocytic syndrome, macrophage activation syndrome, Still's disease, Kawasaki disease, burn injury, systemic granuromatous disease, colitis ulcerosa, Crohn's disease, hypercytokinemia on dialysis, multiple organ failure, bone diseases, cartilage injury and others.
Meanwhile, as compounds which have analogous structures to the structure of the compound according to the present invention, selective FP agonists are disclosed in, for example, International Publication No. 2011/013651 pamphlet (Patent Document 1) and International Publication No. 2012/102355 pamphlet (Patent Document 2), and prostacyclin derivatives are disclosed in, for example, Japanese Patent Laying-Open No. S61-218588 (Patent Document 3) and Japanese Patent Laying-Open No. S55-89261 (Patent Document 4).
However, in these prior art documents, there is found no statement or suggestion about selective EP2 agonists.